Many solid tumors have been found to be responive to treatment with hyperthermia. In some cases treatment with moderate hyperthermia which does not appreciably affect normal tissue can cure or cause regression of tumor. One reason for this preferential sensitivity of tumor tissue to hyperthermia is the difference in structure and functional capabilities of normal and tumor vasculatures. Our laboratory and others have reported that normal and tumor blood vessels differ in their capacities to vasodilate and regulate blood flow following exposure to hyperthermia. Recently our laboratory has obtained evidence that hyperthermia may primarily affect tumor vasculature. Vascular collapse then leads to secondary destruction of tumor cells. The hemorrhagic appearance of heated tumors plus the known association of many tumors with elevated levels of coagulation factors suggests that the marked sensitivity of tumor vasculature to hyperthermia may be a result of intravascular coagulation. We plan to test this hypothesis by determining if elements of the clotting mechanism are involved in vascular collapse following hyperthermia. We hope to ascertain whether treatment with agents which support intravascular clotting will aggravate hyperthermic destruction of tumor vasculature and whether treatment with agents with antagonize intravascular clotting will ameliorate hyperthermic destruction of tumor vasculature. This information will be useful in establishing whether intravascular clotting is the mechanism by which hyperthermia destroys tumor vasculature. It will also establish the feasibility of a cancer therapy regimen which might use agents which enhances coagulation in combination with hyperthermia.